Enzymatic glycosylation of aloesone performed by plant UDP-dependent glycosyltransferases.

Aloesone is a bioactive natural product and biosynthetic precursor of rare glucosides found in rhubarb and some aloe plants including Aloe vera. This study aimed to investigate biocatalytic aloesone glycosylation and more than 400 uridine diphosphate-dependent glycosyltransferase (UGT) candidates, including multifunctional and promiscuous enzymes from a variety of plant species were assayed. As a result, 137 selective aloesone UGTs were discovered, including four from the natural producer rhubarb. Rhubarb UGT72B49 was further studied and its catalytic constants (kcat = 0.00092 ± 0.00003 s-1, KM = 30 ± 2.5 µM) as well as temperature and pH optima (50 °C and pH 7, respectively) were determined. We further aimed to find an efficient aloesone glycosylating enzyme with potential application for biocatalytic production of the glucoside. We discovered UGT71C1 from Arabidopsis thaliana as an efficient aloesone UGT showing a 167-fold higher catalytic efficiency compared to that of UGT72B49. Interestingly, sequence analysis of all the 137 newly identified aloesone UGTs showed that they belong to different phylogenetic groups, with the highest representation in groups B, D, E, F and L. Finally, our study indicates that aloesone C-glycosylation is highly specific and rare, since it was not possible to achieve in an efficient manner with any of the 422 UGTs assayed, including multifunctional GTs and 28 known C-UGTs.

Aloesin ameliorates hypoxic-ischemic brain damage in neonatal mice by suppressing TLR4-mediated neuroinflammation.

BACKGROUND: At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult. MATERIALS AND METHODS: Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking. RESULTS: ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4. CONCLUSION: ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.

Aloesin-loaded chitosan/cellulose-based scaffold promotes skin tissue regeneration.

Skin wound healing and regeneration is very challenging across the world as simple or acute wounds can be transformed into chronic wounds or ulcers due to foreign body invasion, or diseases like diabetes or cancer. The study was designed to develop a novel bioactive scaffold, by loading aloesin to chitosan-coated cellulose scaffold, to cure full-thickness skin wounds. The physiochemical characterization of the scaffold was carried out using scanning electron microscopy (SEM) facilitated by energy-dispersive spectrophotometer (EDS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The results indicated the successful coating of chitosan and aloesin on cellulose without any physical damage. The drug release kinetics confirmed the sustained release of aloesin by showing a cumulative release of up to 88 % over 24 h. The biocompatibility of the aloesin-loaded chitosan/cellulose (AlCsCFp) scaffold was evaluated by the WST-8 assay that confirmed the significantly increased adherence and proliferation of fibroblasts on the AlCsCFp scaffold. The in vivo wound healing study showed that both 0.05 % and 0.025 % AlCsCFp scaffolds have significantly higher wound closure rates (i.e. 88.2 % and 95.6 % approximately) as compared to other groups. This showed that novel composite scaffold has a wound healing ability. Furthermore, histological and gene expression analysis demonstrated that the scaffold also induced cell migration, angiogenesis, re-epithelialization, collagen deposition, and tissue granulation formation. Thus, it is concluded that the aloesin-loaded chitosan/cellulose-based scaffold has great therapeutic potential for being used in wound healing applications in the clinical setting in the future.

New opportunities and perspectives on biosynthesis and bioactivities of secondary metabolites from Aloe vera.

Historically, the genus Aloe has been an indispensable part of both traditional and modern medicine. Decades of intensive research have unveiled the major bioactive secondary metabolites of this plant. Recent pandemic outbreaks have revitalized curiosity in aloe metabolites, as they have proven pharmacokinetic profiles and repurposable chemical space. However, the structural complexity of these metabolites has hindered scientific advances in the chemical synthesis of these compounds. Multi-omics research interventions have transformed aloe research by providing insights into the biosynthesis of many of these compounds, for example, aloesone, aloenin, noreugenin, aloin, saponins, and carotenoids. Here, we summarize the biological activities of major aloe secondary metabolites with a focus on their mechanism of action. We also highlight the recent advances in decoding the aloe metabolite biosynthetic pathways and enzymatic machinery linked with these pathways. Proof-of-concept studies on in vitro, whole-cell, and microbial synthesis of aloe compounds have also been briefed. Research initiatives on the structural modification of various aloe metabolites to expand their chemical space and activity are detailed. Further, the technological limitations, patent status, and prospects of aloe secondary metabolites in biomedicine have been discussed.

Natural Product Aloesin Significantly Inhibits Spore Germination and Appressorium Formation in Magnaporthe oryzae.

This study aims to determine the effects of the natural product aloesin against Magnaporthe oryzae. The results exposed that aloesin had a high inhibitory effect on appressorium formation (the EC50 value was 175.26 µg/mL). Microscopic examination revealed that 92.30 ± 4.26% of M. oryzae spores could be broken down by 625.00 µg/mL of aloesin, and the formation rate of appressoria was 4.74 ± 1.00% after 12 h. M. oryzae mycelial growth was weaker than that on the control. The enzyme activity analysis results indicated that aloesin inhibited the activities of polyketolase (PKS), laccase (LAC), and chain-shortening catalytic enzyme (Aayg1), which are key enzymes in melanin synthesis. The inhibition rate by aloesin of PKS, LAC, and Aayg1 activity was 32.51%, 33.04%, and 43.38%, respectively. The proteomic analysis showed that actin expression was downregulated at 175.62 µg/mL of aloesin, which could reduce actin bundle formation and prevent the polar growth of hyphae in M. oryzae. This is the first report showing that aloesin effectively inhibits conidia morphology and appressorium formation in M. oryzae.

Characterization of the metabolism of aloin A/B and aloesin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.

Identification of Aloe-derived natural products as prospective lead scaffolds for SARS-CoV-2 main protease (Mpro) inhibitors.

In the past two years, the COVID-19 pandemic has caused over 5 million deaths and 250 million infections worldwide. Despite successful vaccination efforts and emergency approval of small molecule therapies, a diverse range of antivirals is still needed to combat the inevitable resistance that will arise from new SARS-CoV-2 variants. The main protease of SARS-CoV-2 (Mpro) is an attractive drug target due to the clinical success of protease inhibitors against other viruses, such as HIV and HCV. However, in order to combat resistance, various chemical scaffolds need to be identified that have the potential to be developed into potent inhibitors. To this end, we screened a high-content protease inhibitor library against Mproin vitro, in order to identify structurally diverse compounds that could be further developed into antiviral leads. Our high-content screening efforts retrieved 27 hits each with > 50% inhibition in our Mpro FRET assay. Of these, four of the top inhibitor compounds were chosen for follow-up due to their potency and drugability (Lipinski's rules of five criteria): anacardic acid, aloesin, aloeresin D, and TCID. Further analysis via dose response curves revealed IC50 values of 6.8 µM, 38.9 µM, 125.3 µM, and 138.0 µM for each compound, respectively. Molecular docking studies demonstrated that the four inhibitors bound at the catalytic active site of Mpro with varying binding energies (-7.5 to -5.6 kcal/mol). Furthermore, Mpro FRET assay kinetic studies demonstrated that Mpro catalysis is better represented by a sigmoidal Hill model than the standard Michaelis-Menten hyperbola, indicating substantial cooperativity of the active enzyme dimer. This result suggests that the dimerization interface could be an attractive target for allosteric inhibitors. In conclusion, we identified two closely-related natural product compounds from the Aloe plant (aloesin and aloeresin D) that may serve as novel scaffolds for Mpro inhibitor design and additionally confirmed the strongly cooperative kinetics of Mpro proteolysis. These results further advance our knowledge of structure-function relationships in Mpro and offer new molecular scaffolds for inhibitor design.

Extraction of Aloesin from Aloe vera Rind Using Alternative Green Solvents: Process Optimization and Biological Activity Assessment.

Aloesin is an aromatic chromone with increasing applications in the cosmetic and health food industries. To optimize its extraction from the Aloe vera leaf rind, the independent variables time (10-210 min), temperature (25-95 °C) and organic solvent composition (0-100%, w/w) were combined in a central composite design coupled with response surface methodology. The solvents consisted of binary mixtures of water with ethanol, propylene glycol, or glycerol. The aloesin levels quantified in each extract were used as response for optimization. The theoretical models were fitted to the experimental data, statistically validated, and used to obtain the optimal extraction conditions. Then, a dose-response analysis of the solid/liquid ratio (S/L) was performed under the optimal conditions determined for each alcohol-water system and revealed that a linear improvement in extraction efficiency can be achieved by increasing the S/L ratio by up to 40 g/L. This analysis also allowed to experimentally validate the predictive models. Furthermore, the aloesin-rich extracts revealed antioxidant activity through thiobarbituric acid reactive substances (TBARS) formation inhibition, antimicrobial effects against bacterial and fungal strains, and no toxicity for PLP2 cells. Overall, this study provided optimal extraction conditions for the recovery of aloesin from Aloe vera rind through an eco-friendly extraction process and highlighted its bioactive potential.

Anti-tyrosinase activity of South African Aloe species and isolated compounds plicataloside and aloesin.

Tyrosinase is the key enzyme in the production of melanin. Tyrosinase inhibitors have gained interest in the cosmetics industry to prevent hyperpigmentation and skin-related disorders by inhibiting melanin production. It has been reported that several Aloe species exhibit anti-tyrosinase efficacy in vitro. In this study, the exudates of thirty-nine South African Aloe species were screened to identify species and compounds with anti-tyrosinase activity. Qualitative screening revealed that twenty-nine Aloe species exhibited tyrosinase inhibition activity with one to three active bands. Quantitative screening was performed for 29 species and expressed as IC50 values. Three species were further analysed and subsequently, aloesin and aloeresin A was isolated from A. ferox and plicataloside from A. plicatilis and A. chabaudii. Aloeresin A was determined to be a substrate of mushroom tyrosinase. Dose-response assays showed that aloesin (IC50 = 31.5 µM) and plicataloside (IC50 = 84.1 µM) exhibited moderate to weak activity. Molecular docking scores for plicataloside were considerably lower than for aloesin (P < 0.01), confirming its lower IC50. Several Aloe species may have potential for the management of hyperpigmentation or as a skin lightening agent. This is the first report showing that plicataloside, present in A. plicatilis and A. chabaudii, exhibits anti-tyrosinase activity.

Two chromones with antimicrobial activity from the leaf latex of Aloe monticola Reynolds.

Aloesin (1) and 7-O-methyl-6'-O-coumaroylaloesin (2) were isolated from the leaf latex of Aloe monticola Reynolds, and their structures determined on the basis of NMR and mass spectroscopic analyses. The antimicrobial activities of the isolated chromones were evaluated against 21 bacterial and 4 fungal strains. Both compounds displayed antibacterial and antifungal effects against most bacterial and fungal strains tested, but their action was more prominent against Salmonella typhi, Shigella dysentery and Staphylococcus aureus (MIC = 10 µg/ml). Acute toxicity tests on mice revealed that neither the latex nor the isolated compounds possess toxicity up to a dose of 2000 mg/kg, signifying an oral LD50 greater than 2000 mg/kg. The results indicate that A. monticola possesses genuine in vitro antimicrobial effect attributed in full or in part to the presence of the isolated chromones in the latex.

[Synthesis of transdermal aloesin loaded zinc oxide nanoparticles and its inhibitory effect on the activity of tyrosinase].

Zinc oxide quantum dots (ZnO QDs) were synthesized by gel-sol method and employed as the transdermal aloesin (Alo) carriers. ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane (APTES). Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs, which were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA). TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution, of which was around 4 nm. The size of Alo NPs increased to around 8 nm due to the surface modification. The intense bands at around 3 400 cm -1 and 1 200 cm -1 in the FTIR spectrum of Alo NPs from the vibration of -OH indicated the linkage of Alo on the surface of ZnO QDs. The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27% and 35.14%, respectively. The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin, which manifested the improvement of the penetration for Alo delivered by ZnO QDs. The pH-controlled drug release behavior in vitro was investigated. At pH 7.4, only a small amount of Alo (1.45% ± 0.21%) had been released after 2 h. In contrast, as incubation at pH 5.0 of which pH was similar to endosomal environment, Alo was released very fast (87.63% ± 0.46% in 2 h) from Alo NPs, confirming that Alo NPs could response to the pH and realize the intracellular drug release. The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner. When the concentration of Alo NPs was 12.5 µg/mL, the inhibition rate was up to 40.32% ± 1.57%. All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.

Aloe Genus Plants: From Farm to Food Applications and Phytopharmacotherapy.

Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among the most economically important medicinal plants and are commonly used in primary health treatment, where they play a pivotal role in the treatment of various types of diseases via the modulation of biochemical and molecular pathways, besides being a rich source of valuable phytochemicals. In the present review, we summarized the recent advances in botany, phytochemical composition, ethnobotanical uses, food preservation, and the preclinical and clinical efficacy of Aloe plants. These data will be helpful to provide future directions for the industrial and medicinal use of Aloe plants.

Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research.

ETHNOPHARMACOLOGICAL RELEVANCE: The African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments. AIM OF THE STUDY: The article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV. The review also provide an account of the in vitro assays, anti-viral activity and phytochemistry of these plants. MATERIALS AND METHODS: Peer-reviewed articles investigating plants with ethnobotanical information for the treatment or management of HIV or HIV-related symptoms from the southern African region were acquired from Science Direct, PubMed central and Google Scholar. The selection criteria was that (1) plants should have a record of traditional/popular use for infectious or viral diseases, HIV treatment or symptoms similar to HIV infection, (2) if not traditionally/popularly used, plants should be closely related to plants with popular use and HIV activity identified by means of in vitro assays, (3) plants should have been identified scientifically, (4) should be native to southern African region and (5) anti-HIV activity should be within acceptable ranges. RESULTS: Many plants in Africa and specifically the southern African region have been used for the treatment of HIV or HIV related symptoms and have been investigated suing various in vitro techniques. In vitro assays using HIV enzymes such as reverse transcriptase (RT), integrase (IN) and protease (PR), proteins or cell-based assays have been employed to validate the use of these plants with occasional indication of the selectivity index (SI) or therapeutic index (TI), with only one study, that progressed to in vivo testing. The compounds identified from plants from southern Africa is similar to compounds identified from other regions of the world, and the compounds have been divided into three groups namely (1) flavonoids and flavonoid glycosides, (2) terpenoids and terpenoid glycosides and (3) phenolic acids and their conjugated forms. CONCLUSIONS: An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.

Aloesin as a medical food ingredient for systemic oxidative stress of diabetes.

Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes and recent advances in diabetes treatments, the reality is that there is no cure for diabetes and its devastating complications. While currently available anti-diabetic therapies are effective in reducing blood glucose level, they are not without associated side effects when they are used for a long term applications. As a result, physicians and patients are inclining more towards to a safer therapy with less serious side effects in the form of medicinal foods and botanical alternatives that are suitable for chronic usage. Aloesin, an Aloe chromone, has previously been formulated with an aloe polysaccharide to give a composition called Loesyn, where it showed significant impact in reducing glycosylated hemoglobin, fasting blood glucose, fructosamine and plasma insulin level in humans. Radical scavenging activities of chromones and polysaccharides from Aloe have also been reported. Here we rationalize the relevance of use of Aloesin alone or in a standardized blend with Aloe polysaccharides, as a potential medical food to manage systemic oxidative stress and/or high blood glucose of diabetes.

Phytochemical constituents and in vitro radical scavenging activity of different Aloe species.

The phytochemical profile of Aloe barbadensis Mill. and Aloe arborescens Mill. was investigated using colorimetric assays, triple quadrupole and time-of-flight mass spectrometry, focusing on phenolic secondary metabolites in the different leaf portions. Hydroxycinnamic acids, several characteristic anthrones and chromones, the phenolic dimer feralolide and flavonoids such as flavones and isoflavones were identified. The stable radical DPPH test and the ORAC assay were then used to determine the in vitro radical scavenging. The outer green rind was the most active, while the inner parenchyma was much less effective. The 5-methylchromones aloesin, aloeresin A and aloesone were the most active among the pure secondary metabolites tested. The results suggest that several compounds are likely to contribute to the overall radical scavenging activity, and indicate that leaf portion must be taken into account when the plant is used for its antioxidant properties.

In vivo safety evaluation of UP780, a standardized composition of aloe chromone aloesin formulated with an Aloe vera inner leaf fillet.

Safety profiles of the aloe chromone aloesin or Aloe vera inner leaf fillet (Qmatrix) as a well tolerated entity have been reported separately. UP780, a standardized composition of aloe chromone formulated with an Aloe vera inner leaf fillet, has shown a significant beneficial effect in lowering blood glucose and improving insulin resistance in human. Here we evaluate the safety of UP780 after a repeated 14 and 90-day oral administration in CD-1 mice. UP780 was given at doses of 100mg/kg/day, 500mg/kg/day and 1000mg/kg/day to groups of 10 male and 10 female for 90days or administered by oral gavage at a dose of 2g/kg/day to groups of 5 male and 5 female for 14days. Body weight, feed consumption, hematology, clinical chemistry and histopathologic evaluation were performed. UP780 at a dose of 1000mg/kg/day or at 2000mg/kg/day produced no treatment-related toxicity or mortality. Body weight gain or feed consumption was similar between groups. There was no test article-related microscopic change. Spontaneously occurring minor changes in clinical chemistry and hematology were observed. However, these changes were limited to one sex or were not dose correlated. UP780 was well tolerated in this strain. A dose of 2000mg/kg/day was identified as the NOAEL (no-observed-adverse-effect-level).

Chemical constituents of Aloe barbadensis Miller and their inhibitory effects on phosphodiesterase-4D.

Aloe barbadensis Mill has been used as food and medicine for a long time. In order to investigate the chemical constituents of A. barbadensis and their inhibitory activities towards phosphodiesterase-4D (PDE4D), 70% methanol extract of the dried A. barbadensis powder was employed. Phytochemical investigation has led to the isolation of three new chromones, 5-(hydroxymethyl)-7-methoxy-2-methylchromone (4), 5-((4E)-2'-oxo-pentenyl)-2-hydroxymethylchromone (6), and 7-hydroxy-5-(hydroxymethyl)-2-methylchromone (7), together with eighteen known compounds. Their chemical structures were determined based on spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS spectrometry. In addition, their inhibition against PDE4D was evaluated using tritium-labeled adenosine 3',5'-cyclic monophosphate ((3)H-cAMP) as the substrate. Inhibition was calculated by the variation of radioactivity after the reaction, and compounds 1-4, 10, and 21 exhibited certain inhibitory activities towards PDE4D, which can provide an explanation why A. barbadensis can serve as anti-inflammatory agents.

A comparative study of baby immature and adult shoots of Aloe vera on UVB-induced skin photoaging in vitro.

Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-ß1 (TGF-ß1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-ß1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-ß1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE.

Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models.

Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 microM of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level.